Charles V acceded to the throne in Milan in 1535, and thus the city entered a period of Spanish rule, spanning almost two centuries. Alessandro Manzoni’s classic work 'The Betrothed' provides a chronicle of this period.

Under Austrian rule in the 1700s, Milan’s cultural life transformed. Teatro alla Scala, famous for Giuseppe Verdi’s debut and other epic events, was completed. Other accomplishments in terms of architecture include the Arco della Pace and many Neo-Classical edifices.

However, Milan suffered from an outbreak of the plague between 1629 and 1631. Frequently called the Great Plague of Milan, this infliction claimed almost 300,000 lives. This was one of the last outbreaks of the centuries-long plague pandemic, which had started with the Black Death.

After the Napoleonic Wars, Milan was annexed into the Cisalpine Republic, the French satellite territory that eventually became the Kingdom of Italy. Later, the city was under Austrian rule as part of the Kingdom of Lombardy-Venetia and soon became a major centre of a nationalist movement for independence.

Austrian rule ended in 1859 by the Kingdom of Sardinia-Piedmont in the Second War of Independence, and was transformed into the Kingdom of Italy two years later. The newly-established Savoy monarchy ushered in an epoch of architectural splendour, an example of which is the Bagatti Valsecchi Museum. Milan also grew significantly, not only in terms of population, but also industrial output, becoming one of the most developed cities in Italy.